SPCS2 (signal peptidase complex subunit 2) is a component of the signal peptidase complex (SPC) that catalyzes cleavage of N-terminal signal sequences from nascent proteins during translocation into the endoplasmic reticulum (ER) lumen 1. The protein enhances SPC enzymatic activity and facilitates interactions between translocation site components, functioning as part of the ER protein processing machinery 1. In disease contexts, SPCS2 dysregulation associates with multiple pathological conditions. SPCS2 was identified as a differentially expressed gene in parathyroid adenomas, suggesting involvement in parathyroid tumorigenesis 2. In primary Sjögren's syndrome, SPCS2 is enriched in plasma cell modules alongside B-cell receptor signaling components, linking it to autoantibody production and chr11 inflammation 3. SPCS2 overexpression occurs in pediatric acute myeloid leukemia with primary induction failure, emerging as a potential biomarker for chemoresistance 4. Additionally, SPCS2 variants impair U12-type intron splicing in isolated growth hormone deficiency, demonstrating tissue-specific consequences of defective mRNA processing 5. SPCS2 also appears as a miR-486-5p target in endothelial dysfunction 6 and interacts with hepatitis C virus assembly proteins 7. Clinically, SPCS2 dysregulation marks multiple malignancies and genetic disorders, positioning it as a potential therapeutic target and diagnostic biomarker.