SPCS1 (signal peptidase complex subunit 1) is a critical component of the endoplasmic reticulum signal peptidase complex that plays essential roles in viral protein processing and disease pathogenesis. The protein is required for post-translational processing of structural proteins in multiple flaviviruses, including West Nile, Dengue, Zika, Yellow Fever, Japanese encephalitis, and hepatitis C viruses 1. SPCS1 specifically facilitates cleavage of flaviviral structural proteins prM and E, which is necessary for proper virion assembly and secretion 1. In Japanese encephalitis virus, SPCS1 interacts with nonstructural protein NS2B through transmembrane domains, regulating viral assembly without affecting cell entry, RNA replication, or translation 2. For hepatitis C virus, SPCS1 facilitates E2-p7 processing by the signal peptidase complex, which is crucial for viral assembly efficiency 3. Beyond viral infections, SPCS1 has been implicated in multiple diseases. It serves as a predictive biomarker for Alzheimer's disease with depression 4, shows differential expression in Alzheimer's disease brain tissue 5, and is subject to cis-acting regulatory polymorphisms associated with osteoarthritis susceptibility 6. The protein's preferential processing of specific protein cargo makes it a potential therapeutic target for flavivirus infections 1.