Soluble resistance-related calcium-binding protein participates in multiple diseases via protein-protein interactions.

Soluble resistance-related calcium-binding protein (sorcin), a 22 kDa penta-EF-hand protein, has been intensively studied in cancers and multidrug resistance over a prolonged period. Sorcin is widely distributed in tissues and participates in the regulation of Ca2+ homeostasis and Ca2+-dependent signaling. Protein-protein interactions (PPIs) are essential for regulating protein functions in almost all biological processes. Sorcin interaction partners tend to vary in type, including Ca2+ receptors, Ca2+ transporters, endoplasmic reticulum stress markers, transcriptional regulatory elements, immunomodulation-related factors, and viral proteins. Recent studies have shown that sorcin is involved in a broad range of pathological conditions, such as cardiomyopathy, type 2 diabetes mellitus, neurodegenerative diseases, liver diseases, and viral infections. As a multifunctional cellular protein, in these diseases, sorcin has a role by interacting with or regulating the expression of other proteins, such as sarcoplasmic reticulum/endoplasmic reticulum Ca2+ ATPase, ryanodine receptors, presenilin 2, L-type Ca2+ channels, carbohydrate-responsive element-binding protein, tau, α-synuclein, signal transducer and activator of transcription 3, HCV nonstructural 5A protein, and viral capsid protein 1. This review summarizes the roles that sorcin plays in various diseases, mainly via different PPIs, and focuses principally on non-neoplastic diseases to help acquire a more comprehensive understanding of sorcin's multifunctional characteristics.