PCSK7 is a serine endoprotease that cleaves proproteins at paired basic amino acids (RXXX[KR]R motif) in the constitutive secretory pathway and trans-Golgi network 1. Beyond its canonical enzymatic function, PCSK7 exhibits noncanonical roles in protein processing, including cleavage of apolipoprotein B and Syncytin-2 12. PCSK7 plays multifaceted roles in metabolic and immune regulation. In hepatocytes, PCSK7 modulates lipogenesis and triglyceride metabolism; genetic variants (rs236918, rs236911, rs508487) associate with dyslipidemia, increased triglycerides, reduced HDL cholesterol, and nonalcoholic fatty liver disease severity 34. PCSK7 expression is negatively regulated by miR-125a-5p, miR-143-3p, and miR-409-3p 5. In immune cells, PCSK7 enrichment in CD8+ T cells correlates with immune checkpoint protein expression (LAG3, CTLA4, PD1, TIGIT); PCSK7 deletion reduces checkpoint protein surface levels and enhances antitumor immunity 6. In macrophages, PCSK7 activates TNF-α/JNK signaling, intensifying post-myocardial infarction inflammation 7. PCSK7 also regulates iron homeostasis, with genetic associations to soluble transferrin receptor levels 8. Notably, Pcsk7 knockout mice are healthy and fertile, suggesting PCSK7 inhibition is potentially safe for treating metabolic dysfunction-associated steatotic liver disease, dyslipidemia, cardiovascular disease, and cancer 1.