OSBPL2 (oxysterol binding protein like 2) functions as an intracellular lipid transport protein that mediates cholesterol and phospholipid trafficking between cellular compartments 1. The protein binds various sterols including cholesterol, 22(R)-hydroxycholesterol, and 25-hydroxycholesterol, as well as phospholipids such as phosphatidylinositol-4,5-bisphosphate and phosphatidic acid 1. OSBPL2 increases plasma membrane cholesterol levels while decreasing phosphatidylinositol-4,5-bisphosphate levels in cell membranes. Mechanistically, OSBPL2 interacts with autophagy proteins and maintains endolysosomal homeostasis 2. The protein also directly interacts with PLCB3, inhibiting its ubiquitination and thereby stabilizing it, which is crucial for proper keratinocyte function 3. Disease-wise, OSBPL2 mutations cause autosomal dominant hearing loss (DFNA67), characterized by progressive hearing loss with cochlear hair cell degeneration and hypercholesterolemia 4. Frameshift mutations lead to toxic protein accumulation, defective autophagy, and hearing impairment 2. Additionally, compound heterozygous OSBPL2 variants cause Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome through enhanced PLCB3 degradation leading to epidermal hyperkeratosis 3. Clinically, rapamycin shows therapeutic potential for DFNA67 by reducing mutant protein accumulation 2.