Ribosome biogenesis is a highly regulated process that requires the participation of several accessory proteins that participates in the cytoplasmic last maturation step before entering the pool of translating ribosomes. One of these accessory proteins is the GTPase Elongation Factor-like 1 (EFL1), a homologue of the elongation factor 2 (EF-2). EFL1, together with SBDS (yeast Sdo1), evict the anti-association factor eIF6 (yeast Tif6) from the surface of the 60S subunit, allowing mature ribosome assembly. Defects in the function of any of these two proteins lead to a disease called Shwachman-Diamond Syndrome (SDS). Mutations prevent the release of eIF6 from the 60S subunit, with the consequent imbalance of mature 60S subunits entering the pool of active translating 80S ribosomes and a decrease in global translation. EFL1 is a molecular motor that adopts at least four distinct conformations in solution regulated by SBDS and guanine nucleotides whose malfunction in the SDS has been scarcely studied. The malfunction of the non-synonymous mutations in EFL1 has been scarcely studied, with little effect on its catalytic activity or fold. We used Isothermal Titration Calorimetry to gain further insights into the malfunction of Efl1 mutations. We characterised the binding energetics of S. cerevisiae Efl1 R1086Q equivalent to EFL1 R1095Q reported in patients with SDS. The data presented exhibits a different structural and energetic response in the yeast mutant Efl1 R1086Q compared to that previously reported Efl1 wild type. The heat capacity change (ΔCp) and conformational binding entropy of the complexes formed between the mutant and the wild type proteins showed opposite values suggesting they adopt different conformations. We conclude that mutation R1086Q profoundly disrupts the internal rearrangements necessary to elicit a similar conformational change as that in native EFL1.