CPNE5 encodes a calcium-dependent phospholipid-binding protein with diverse physiological roles. During neural development, CPNE5 is expressed in neural progenitor cells and differentiating neurons, particularly in the embryonic cortex and ganglionic eminence, suggesting involvement in central nervous system development 1. In retinal ganglion cells, CPNE5 is regulated by Brn3 transcription factors and may participate in dendrite and axon formation 2. Genetically, CPNE5 variants show significant clinical associations. Six SNPs in CPNE5 are associated with both alcohol dependence and obesity in Caucasian populations, suggesting shared genetic components linking these conditions 3. A CPNE5 variant (rs3213537) has been identified as a promising genetic marker for power-related athletic performance 4. Additionally, a rare variant gene set mapped to CPNE5 exhibits interaction with excessive daytime sleepiness in sleep apnea patients 5. In cancer contexts, CPNE5 expression serves as a prognostic biomarker. Low CPNE5 expression in esophageal squamous cell carcinoma independently predicts shorter overall survival and increased local recurrence risk 6. Conversely, high CPNE5 expression correlates with favorable outcomes in multiple myeloma, predicting longer event-free and overall survival 7. Recently, CPNE5 has emerged as critical for vascular integrity. Reduced plasma CPNE5 levels in sepsis patients correlate with vascular leakage, organ injury, and mortality, with CPNE5-knockout mice showing increased sepsis-induced morbidity and lethality 8.