SEC62 is a transmembrane endoplasmic reticulum (ER) protein that mediates post-translational transport of presecretory polypeptides across the ER membrane 1. SEC62 acts as a targeting receptor for small presecretory proteins with short signal peptides, positioning them into the SEC61 translocon channel to facilitate translocation into the ER lumen. Beyond its canonical ER translocation function, SEC62 plays emerging roles in cellular quality control and disease pathogenesis. SEC62 participates in reticulophagy, the selective autophagic degradation of ER subdomains, functioning as a reticulophagy receptor 2. In this context, SEC62 facilitates autophagy-mediated lysosomal degradation of impaired ER regions, particularly during STING1-mediated selective autophagy in response to nutrient deprivation and viral infection 3. SEC62 also regulates intracellular calcium homeostasis through direct interaction with the SEC61 channel and contributes to cellular compensation of ER stress 1. Clinically, SEC62 overexpression correlates with cancer progression and chemoresistance. In colorectal cancer, SEC62 upregulation promotes cancer stemness and chemoresistance by stabilizing β-catenin and activating Wnt/β-catenin signaling 4. In cholangiocarcinoma, SEC62-mediated ER-phagy drives cisplatin resistance through protein degradation pathways 5. These findings position SEC62 as a potential therapeutic target for improving cancer treatment outcomes.