Life Sci. 2026 Oct 2:124718. doi: 10.1016/j.lfs.2026.124718. Online ahead of print.
ABSTRACT
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.
PMID:42826880 | DOI:10.1016/j.lfs.2026.124718