Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 or NPC2 deficiency models showed that the function of these two proteins within lysosomes are linked closely. NPC2 is also named human epididymis-specific protein 1 (HE1), defects of which are the cause of Niemann-Pick disease type C2, characterized as a lysosomal storage disorder that affects the viscera and the central nervous system. Recent finding suggests that NPC2 may serve as a novel intracrine/autocrine factor that controls adipocyte differentiation and function as well as potential therapeutic target for the treatment of type 2 diabetes and related metabolic disorders.