SEC63 is a protein translocation regulator mediating cotranslational and post-translational transport of precursor polypeptides across the endoplasmic reticulum (ER) 12. It functions as an auxiliary component of the SEC62/SEC63 complex, cooperating with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 translocon channel, triggering channel opening for translocation 2. SEC63 is essential for efficient polycystin-1 (PKD1) biogenesis and trafficking to primary cilia 3. SEC63 mutations are associated with autosomal dominant polycystic liver disease (ADPLD), characterized by severe liver cysts with minimal kidney involvement 45. Loss-of-function SEC63 variants result in defective polycystin-1 maturation and trafficking, the central determinant of cyst pathogenesis 3. SEC63 represents one of two major genes causing ADPLD, alongside PRKCSH 5. Beyond polycystic disease, SEC63 regulates metabolic reprogramming in hepatocellular carcinoma through ER stress-responsive pathways, with elevated expression correlating to unfavorable prognosis 6. Genetic testing incorporating SEC63 and related ER protein biosynthetic pathway genes (SEC61B, GANAB, DNAJB11, ALG8, ALG9) is recommended for comprehensive diagnostic evaluation of polycystic kidney and liver diseases 75.