To obtain insights into the physiological role of GBA2 and into the etiology of SPG46 and MSS, we previously modeled ten SPG46-associated GBA2 mutations in the cDNA coding for human GBA2, and found that single amino acid-substituted and C-terminally truncated forms of GBA2 failed to cleave its substrate [22]. Here, GBA2 is linked to Marinesco-Sjogren syndrome.