Found in all kingdoms of life, small heat shock proteins (sHSPs) are molecular chaperones whose primary function is to maintain aggregation-prone proteins in a soluble state. Most mammalian sHSPs exist as highly dynamic, polydisperse oligomers. The basic structural unit is a dimer formed via a conserved central α-crystallin domain. The highly divergent N-terminal domain (NTD) is responsible for the diverse and unique oligomerization properties of sHSPs. NTDs are predicted to be disordered and are highly hydrophobic, making them intractable structural targets individually. Therefore, NTDs must be investigated in the context of full-length sHSP oligomers, which are themselves refractory to traditional structural methods. Phosphorylation of NTD residues is an essential stress response that alters both function and oligomeric properties in some human sHSPs. HSPB1 phosphorylation yields a distribution of smaller oligomers, with a substantial population belonging to the basic dimeric unit. Additionally, inherited mutations in HSPB1 N-terminal residues are associated with serious neuropathies such as Charcot-Marie-Tooth disease. We seek to compare local and global structures of dimeric HSPB1 and intermediate oligomeric/phosphorylation states to its WT oligomeric counterpart. Towards this end, we developed a mutant that forms discrete dimers (HSPB1dim), which is amenable to solution NMR, to represent a fully phosphorylated and fully dispersed state of the protein. We use a variety of complementary biophysical approaches including hydrogen-deuterium exchange MS and CD spectroscopy to compare secondary structure, methyl-TROSY NMR to observe individual residues in the larger oligomers, and multi-angle light-scattering to estimate numbers of subunits. We aim to define structural mechanisms by which NTD disease-associated mutations and stress-induced phosphorylation alter chaperone activity and oligomeric propensity of HSPB1. Our results identify key differences that may reveal the highly plastic sequence-oligomeric structure relationship in sHSPs and implicated in their associated diseases.