Calmodulin-1

Calmodulin-1 (CALM1) is a small, ubiquitous calcium-binding protein that mediates calcium signal transduction by regulating the activity of numerous enzymes, ion channels, and proteins upon calcium binding (UniProt: P0DP23). It activates key signaling molecules including calmodulin-dependent protein kinase type II and protein phosphatases, and modulates voltage-dependent calcium channels and potassium channels. Calmodulin also participates in centrosome cycle regulation and serves as a sensor for endoplasmic reticulum-organelle contacts (UniProt: P0DP23).

CALM1 is primarily known for cardiac dysfunction. Mutations in CALM1 cause catecholaminergic polymorphic ventricular tachycardia (CPVT4) and long QT syndrome 14 (LQT14), both autosomal dominant arrhythmogenic disorders that present with stress-induced syncope and sudden cardiac death (UniProt: P0DP23).

In Alzheimer's disease, CALM1 is significantly downregulated in post-mortem brain tissue compared to age-matched controls. Proteomic analysis by TMT-labeled mass spectrometry revealed a mean log2 fold-change of −0.83 across subcellular fractions (Chaparral AD proteomics). This downregulation may reflect impaired calcium signaling and dysregulated synaptic or cellular homeostasis in AD pathology.