APLP2 is a transmembrane protein with multiple cellular functions, primarily involved in proteolytic processing and cellular signaling. As a member of the APP family, APLP2 is predominantly cleaved by β-secretase and γ-secretase in the human brain 1, with these cleavage events suggesting a role in central nervous system function similar to APP. APLP2 functions as a negative regulator of TGF-β signaling by interfering with TGFBR2-Hsp90 interactions, leading to TGFBR2 degradation and desensitization to TGF-β stimulation 2. The protein is upregulated during neuronal differentiation in response to retinoic acid 3, supporting its involvement in neuronal development. APLP2 expression is regulated by housekeeping-like promoter elements lacking TATA boxes 4. Genetically, APLP2 polymorphisms (rs2054247 and rs747180) are associated with elevated serum total cholesterol and LDL-cholesterol levels 5, linking APLP2 to lipid metabolism and cardiovascular risk. In cancer biology, APLP2 promotes hepatocellular carcinoma progression by regulating apoptosis and cell cycle progression 6. These findings establish APLP2 as a pleiotropic protein with roles in neurodegeneration, metabolic regulation, and cancer biology, though the functional relationships between these processes remain incompletely understood.