SERINC2: From membrane lipid synthesis to human disease.

AIMS: This review aims to summarize current evidence on the role of serine incorporator 2 (SERINC2) in human disease, focusing on how its function in serine-associated membrane lipid biosynthesis-particularly phosphatidylserine and sphingolipid metabolism-may contribute to disease-associated phenotypes across cancer, cardiovascular disease, and neuropsychiatric disorders.

MATERIALS AND

METHODS

Relevant studies were identified through PubMed, Scopus, and Web of Science using search terms including "SERINC2," "serine incorporator," "phosphatidylserine," and "sphingolipid," alone and in combination with disease-related terms. Original research articles and relevant reviews published up to 2026 were included and prioritized according to the directness of their functional evidence for SERINC2.

KEY FINDINGS: In selected cancers, particularly lung adenocarcinoma and cervical cancer, SERINC2 has been associated with tumor cell proliferation, migration, and metabolic adaptation, whereas evidence in glioma remains largely association-based and thyroid cancer is supported by preliminary cell-line studies. In cardiovascular disease, SERINC2 has been implicated in pathological cardiac hypertrophy and septic cardiomyopathy through lysosome-associated nutrient sensing (amino acid/mTORC1) and Akt/GSK-3β-associated survival signaling, respectively. In neuropsychiatric disorders, genetic and expression-based evidence links SERINC2 to membrane-related neural processes, although direct mechanistic validation remains limited.

SIGNIFICANCE: Current evidence supports SERINC2 as an emerging, context-dependent disease-associated membrane protein whose membrane lipid regulatory functions may influence disease phenotypes. Clarifying tissue-specific mechanisms will determine whether SERINC2-associated pathways have clinical biomarker or therapeutic relevance.