AHNAK: The quiet giant in calcium homeostasis

The phosphoprotein AHNAK is a large, ubiquitously expressed scaffolding protein involved in mediating a host of protein-protein interactions. This enables AHNAK to participate in various multi-protein complexes thereby orchestrating a range of diverse biological processes, including tumour suppression, immune regulation and cell architecture maintenance. A less studied but nonetheless equally important function occurs in calcium homeostasis. It does so by largely interacting with the L-type voltage-gated calcium channel (LVGCC) present in the plasma membrane of excitable cells such as muscles and neurons. Several studies have characterized the underlying basis of AHNAK's functional role in calcium channel modulation, which has led to a greater understanding of this cellular process and its associated pathologies. In this article we review and examine recent advances relating to the physiological aspects of AHNAK in calcium regulation. Specifically, we will provide a broad overview of AHNAK including its structural makeup and its interaction with several isoforms of LVGCC, and how these molecular interactions regulate calcium modulation across various tissues and their implication in muscle and neuronal function.