Sufficient food supply is critically important to humans, and food security will be particularly challenging in view of the ever-growing world population, decreasing arable cropland, and global warming. To meet the challenges, most crop geneticists think it will be necessary to enrich the cultivated gene pool for breeding programs, and thus equally important to increase our understanding of the underlying genetic and molecular mechanism for grain yield. However, crop yield is a complex trait that is controlled simultaneously by multiple genes (i.e., quantitative trait loci [QTLs]) and heavily influenced by the surrounding environment; hence, to dissect such a complex trait into component contributory traits is necessary. Seed size (weight) is an essential yield component trait, and the past two decades have witnessed the identification of several hundred grain shape QTLs in rice; however, the genetic and molecular regulatory network of these QTLs remains largely unknown. Increasing lines of experimental evidence suggested that the plant hormone brassinosteroids (BRs) play a key role in seed size (weight) and hence crop yield regulation. Here, I briefly discuss the recent progress on how BR biosynthesis and signaling pathway have an impact on the important agronomic trait in crops. A major QTL for grain width on chromosome 5 (GW5, also called qSW5, or GSE5; hereafter called GW5) in rice was fine mapped by independent research groups and reported to be closely associated with a 1212-bp DNA deletion fragment that caused decreased GW5 expression and increased grain width (Shomura et al., 2008Shomura A. Izawa T. Ebana K. Ebitani T. Kanegae H. Konishi S. Yano M. Deletion in a gene associated with grain size increased yields during rice domestication.Nat. Genet. 2008; 40: 1023-1028Crossref PubMed Scopus (683) Google Scholar, Weng et al., 2008Weng J. Gu S. Wan X. Gao H. Guo T. Su N. Lei C. Zhang X. Cheng Z. Guo X. et al.Isolation and initial characterization of GW5, a major QTL associated with rice grain width and weight.Cell Res. 2008; 18: 1199-1209Crossref PubMed Scopus (513) Google Scholar, Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar). Most importantly, significant human selection has been taking place at the GW5 deletion during rice domestication, likely due to artificial selection for breeding high-yield varieties (Shomura et al., 2008Shomura A. Izawa T. Ebana K. Ebitani T. Kanegae H. Konishi S. Yano M. Deletion in a gene associated with grain size increased yields during rice domestication.Nat. Genet. 2008; 40: 1023-1028Crossref PubMed Scopus (683) Google Scholar). More interestingly, Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar found that, in addition to the aforementioned 1212-bp deletion that is present mainly in japonica varieties, a 950-bp DNA deletion is also closely linked to grain width alteration that prevails in indica varieties; also, the three major haplotypes of GW5 identified in cultivated rice could have originated from different wild accessions. An interesting question remains, therefore, as to why the rice subspecies indica and japonica use different GW5 haplotypes to enlarge grain size. Transgenic plants with loss of function of the candidate gene LOC_Os05g09520 by a CRISPR/Cas9 strategy produced a wider grain, while upregulated expression level of the gene bore a narrower grain (Figure 1; Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar), suggesting that GW5 exerts a negative effect on grain width. Sequence analysis indicated that the GW5 is a domestication-related gene encoding a protein with two IQ calmodulin-binding motifs (Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar). GW5 could physically interact with the rice calmodulin OsCaM1-1 (Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar). In previous studies, the GW5 gene has been described to encode an unknown protein that interacts with ubiquitin (i.e., so-called ubiquitin-related protein) (Shomura et al., 2008Shomura A. Izawa T. Ebana K. Ebitani T. Kanegae H. Konishi S. Yano M. Deletion in a gene associated with grain size increased yields during rice domestication.Nat. Genet. 2008; 40: 1023-1028Crossref PubMed Scopus (683) Google Scholar, Weng et al., 2008Weng J. Gu S. Wan X. Gao H. Guo T. Su N. Lei C. Zhang X. Cheng Z. Guo X. et al.Isolation and initial characterization of GW5, a major QTL associated with rice grain width and weight.Cell Res. 2008; 18: 1199-1209Crossref PubMed Scopus (513) Google Scholar); however, Liu et al. and Duan et al. have independently confirmed that its neighboring gene turned out be the viable candidate, which actually encodes a calmodulin-binding protein. However, it remains unclear whether the calcium signaling pathway is indeed involved in GW5 regulation of grain size and how it works. Furthermore, using a carboxyl-terminal fragment of GW5 as the bait to screen a yeast two-hybrid library, GSK2 was identified as a viable interacting partner of GW5, which was confirmed by BiFC and pull-down assays (Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar). It is known that GSK2 is a rice ortholog of the Arabidopsis GSK3/SHAGGY-like kinase BIN2 and functions as a negative regulator of BR signaling in rice. Consistently, in the lamina joint inclination assays, transgenic rice plants overexpressing GW5 in the genetic background of GSK2 RNAi transgene greatly enhanced the phenotypes, which exhibited hypersensitivity to exogenously applied brassinolides (Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar). In addition, a series of biochemical analyses indicated that GW5 could repress the kinase activity of GSK2 toward OsBZR1 and DLT, resulting in accumulation of their unphosphorylated forms and altered BR signaling (Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar). Therefore, as proposed by the authors, GW5 might be a positive regulator of the BR signaling pathway in regulating grain width and weight in rice. BRs are a class of growth-promoting steroidal hormones that were initially isolated from rapeseed (Brassica napus) pollen, which are crucial for normal growth and development, such as plant height, leaf angle, panicle architecture, and seed size (Wu et al., 2016Wu Y. Fu Y. Zhao S. Gu P. Zhu Z. Sun C. Tan L. CLUSTERED PRIMARY BRANCH1, a new allele of DWARF11, controls panicle architecture and seed size in rice.Plant Biotechnol. J. 2016; 14: 377-386Crossref PubMed Scopus (86) Google Scholar). To date, several rice BR biosynthesis mutants that bear seeds of reduced length have been functionally characterized, such as d11 (dwarf11/cpb1), d2 (dwarf2/smg11), brd1 (BR-deficient dwarf1), and brd2 (BR-deficient dwarf2) (Figure 1; Hong et al., 2002Hong Z. Ueguchi-Tanaka M. Shimizu-Sato S. Inukai Y. Fujioka S. Shimada Y. Takatsuto S. Agetsuma M. Yoshida S. Watanabe Y. et al.Loss-of-function of a rice brassinosteroid biosynthetic enzyme, C-6 oxidase, prevents the organized arrangement and polar elongation of cells in the leaves and stem.Plant J. 2002; 32: 495-508Crossref PubMed Scopus (282) Google Scholar, Hong et al., 2005Hong Z. Ueguchi-Tanaka M. Fujioka S. Takatsuto S. Yoshida S. Hasegawa Y. Ahikari M. Kitano H. Matsuoka M. The rice brassinosteroid-deficient dwarf2 mutant, defective in the rice homolog of Arabidopsis DIMINUTO/DWARF1, is rescued by the endogenously accumulated alternative bioactive brassinosteroid, dolichosterone.Plant Cell. 2005; 17: 2243-2254Crossref PubMed Scopus (238) Google Scholar, Fang et al., 2016Fang N. Xu R. Huang L. Zhang B. Duan P. Li N. Luo Y. Li Y. SMALL GRAIN 11 controls grain size, grain number and grain yield in rice.Rice. 2016; 9: 64-74Crossref Scopus (70) Google Scholar, Wu et al., 2016Wu Y. Fu Y. Zhao S. Gu P. Zhu Z. Sun C. Tan L. CLUSTERED PRIMARY BRANCH1, a new allele of DWARF11, controls panicle architecture and seed size in rice.Plant Biotechnol. J. 2016; 14: 377-386Crossref PubMed Scopus (86) Google Scholar). Similarly, genes affecting BR perception and signaling have also been shown to control grain size in rice plants; for example, the rice d61 mutant produced shorter grain and was less sensitive to exogenous BR, compared with the wild-type, most likely caused by loss of function of the rice ortholog of the BR receptor BRI1 in Arabidopsis (Yamamuro et al., 2000Yamamuro C. Ihara Y. Wu X. Noguchi T. Fujioka S. Takatsuto S. Ashikari M. Kitano H. Matsuoka M. Loss of function of a rice brassinosteroid insensitive1 homolog prevents internode elongation and bending of the lamina joint.Plant Cell. 2000; 12: 1591-1605Crossref PubMed Scopus (554) Google Scholar). This is also exemplified by the OsmiR397-OsLAC module, wherein the laccase-like protein OsLAC was targeted by OsmiR397; transgenic plants overexpressing OsmiR397 bore enlarged grain and were much more sensitive to exogenously applied BR treatment, while those plants overexpressing OsLAC reduced grain size and were almost insensitive to the same treatment (Figure 1; Zhang et al., 2013Zhang Y. Yu Y. Wang C. Li Z. Liu Q. Xu J. Liao J. Wang X. Qu L. Chen F. et al.Overexpression of microRNA OsmiR397 improves rice yield by increasing grain size and promoting panicle branching.Nat. Biotechnol. 2013; 31: 848-852Crossref PubMed Scopus (292) Google Scholar). Furthermore, a grain-length QTL GS2/GL2 was recently shown to encode a plant-specific transcription factor OsGRF4 (growth regulating factor 4) that targeted by miR396; perturbation of the binding site of OsGRF4 by miR396 caused elevated OsGRF4 expression, and consequently upregulated the expression of the BR-induced genes (Hu et al., 2015Hu J. Wang Y. Fang Y. Zeng L. Xu J. Yu H. Shi Z. Pan J. Zhang D. Kang S. et al.A rare allele of GS2 enhances grain size and grain yield in rice.Mol. Plant. 2015; 8: 1455-1465Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar, Che et al., 2016Che R. Tong H. Shi B. Liu Y. Fang S. Liu D. Xiao Y. Hu B. Liu L. Wang H. et al.Control of grain size and rice yield by GL2-mediated brassinosteroid responses.Nat. Plants. 2016; 2: 1-7Google Scholar). Moreover, GSK2 was found to interact with and repress the transcription activation activity of OsGRF4 (Che et al., 2016Che R. Tong H. Shi B. Liu Y. Fang S. Liu D. Xiao Y. Hu B. Liu L. Wang H. et al.Control of grain size and rice yield by GL2-mediated brassinosteroid responses.Nat. Plants. 2016; 2: 1-7Google Scholar). In addition, a major QTL for soybean seed weight encoding a putative phosphatase 2C (PP2C) was very recently characterized, and similar to the scenario for rice GW5, PP2C from the wild allele could interact with and enhance the accumulation of dephosphorylated GmBZR1 (soybean BZR1 ortholog) (Lu et al., 2017Lu X. Xiong Q. Cheng T. Li Q.-T. Liu X.-L. Bi Y.-D. Li W. Zhang W.-K. Ma B. Lai Y.-C. et al.A PP2C-1 allele underlying a quantitative trait locus enhances soybean 100-seed weight.Mol. Plant. 2017; 10: 670-684Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). It is of interest to note that the outer epidermal cell size in spikelet hulls of BR synthesis mutants d2 or d11 were smaller, while those of overexpression of either the D2 or D11 gene became significantly larger than the wild-type controls in rice plants (Fang et al., 2016Fang N. Xu R. Huang L. Zhang B. Duan P. Li N. Luo Y. Li Y. SMALL GRAIN 11 controls grain size, grain number and grain yield in rice.Rice. 2016; 9: 64-74Crossref Scopus (70) Google Scholar, Wu et al., 2016Wu Y. Fu Y. Zhao S. Gu P. Zhu Z. Sun C. Tan L. CLUSTERED PRIMARY BRANCH1, a new allele of DWARF11, controls panicle architecture and seed size in rice.Plant Biotechnol. J. 2016; 14: 377-386Crossref PubMed Scopus (86) Google Scholar), suggesting that BR might control grain size via altering cell expansion in spikelet hulls. Interestingly, GW5 (or other factors such as miR397) regulates grain size by restricting an increase in cell number (Duan et al., 2017Duan P. Xu J. Zeng D. Zhang B. Geng M. Zhang G. Huang K. Huang L. Xu R. Ge S. et al.Natural variation in the promoter of GSE5 contributes to grain size diversity in rice.Mol. Plant. 2017; 10: 685-694Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, Liu et al., 2017Liu J. Chen J. Zheng X. Wu F. Lin Q. Heng Y. Tian P. Cheng Z. Yu X. Zhou K. et al.GW5 acts in the brassinosteroid signaling pathway to regulate grain width and weight in rice.Nat. Plants. 2017; 3: 17043Crossref PubMed Scopus (300) Google Scholar). To better understand the mechanism underlying BR regulation of seed size, it would be worth investigating how GW5 works in the BR signaling pathway. Despite the progress, the role of BRs in regulating seed size needs to be further dissected, and the genetic regulatory networks among these seed-size regulators also remain to be determined.