TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting.

Introduction: Intensive and detailed investigations of the molecular function and cellular role of mammalian transient receptor potential canonical (TRPC) channels started back in the early 90^th of the past century. Initial TRPC research was fueled by high hopes to resolve fundamental questions of cellular Ca²⁺ signaling. To date, we have learned important lessons in TRPC channel biology and biophysics, while little progress has been made in terms of therapeutic concepts.

Areas covered: This is a critical account of recent progress in building a solid mechanistic basis for therapeutic interventions utilizing TRPC3 as a target. I focus on hurdles and key issues to be resolved, thereby drafting a list of essential scientific 'to-dos' on the way toward drugging of TRPC3.

Expert opinion: Recent advances in the molecular physiology of TRPC3 include unveiling its lipid sensing machinery and the channels´ ability to serve spatiotemporally diverse Ca²⁺ signaling in a cell type- and context-dependent manner. The ongoing development of technology for high-precision manipulation of the channel opens up a view on novel therapeutic strategies. It is now to unravel the complex role of TRPC3 in human physiopathology, to pinpoint the channels´ therapeutic relevance, and to further refine technologies for targeted interventions.