SBF2 encodes a guanine nucleotide exchange factor (GEF) that activates RAB21 and possibly RAB28 by promoting GDP-to-GTP exchange, converting inactive Rab proteins to their active forms 12. During starvation-induced autophagy, SBF2 activates RAB21, which regulates the SNARE protein VAMP8 to facilitate autophagosome-lysosome fusion 2. SBF2 also acts as an adapter for the phosphatase MTMR2, enhancing its catalytic activity toward phosphatidylinositol lipids. Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), an autosomal recessive sensorimotor neuropathy characterized by demyelination and excess myelin outfoldings 3. Disease-associated mutations lead to shortened or truncated proteins, suggesting loss-of-function mechanisms 4. CMT4B2 typically manifests in the first decade with predominantly motor symptoms and moderate disease progression, with neuropathy >90% penetrant by age 10 years 3. Glaucoma, previously considered a hallmark feature, is absent in ~40% of CMT4B2 cases but may develop with age, warranting lifelong intraocular pressure monitoring 3. SBF2 shows broad tissue expression with cytoplasmic localization 4.