Interstitial cells of Cajal in health and disease: A comparative review in humans and animals

Interstitial Cells of Cajal (ICCs) are critical modulators of gastrointestinal motility due to their dual roles of initiating slow waves and providing the interlinking connections to enteric neurotransmission within the syncytium known as the SIP, consisting of smooth muscle cells, ICCs, and platelet derived growth factor- α (PDGFRα+) cells. Experimental and clinical evidence consistently demonstrates that ICC loss or dysfunction, whether due to quantitative depletion or functional impairment, is strongly associated with motility disorders such as gastroparesis, chronic constipation, and pseudo-obstruction, as well as veterinary conditions including equine colic and congenital disorders in young animals. Advances in diagnostic tools, including ANO1 immunostaining, live-cell calcium imaging, and genetic analysis, have significantly improved our ability to characterise ICC networks. Therapeutically, while current management relies mainly on prokinetic drugs and supportive care, future strategies such as stem cell–based regenerative therapies, organoid technology, and molecular targeting of ANO1 channels and c-Kit signalling pathways offer promising avenues for restoring ICC function and improving outcomes in both veterinary and human medicine. This review provides an overview of ICC pathophysiology and highlights recent progress in diagnostic and therapeutic developments, with particular emphasis on comparative evidence across human and veterinary medicine to identify shared mechanisms and translational opportunities.