Transient Receptor Potential Canonical (TRPC) proteins assemble to form channels that enable influx of calcium and sodium ions. There are six TRPC proteins in humans but more than six TRPC channels may arise because of heteromers amongst TRPCs and other TRP proteins. The proteins are widely expressed and have multiple functions throughout the peripheral and central systems of the body. Modulators of the channels include lipids, redox factors, and agonists at G-protein-coupled and tyrosine kinase receptors. My research addresses fundamental understanding of how and why cells control calcium ion entry in vascular biology; particularly in adaptive processes, human disease, and therapeutics. TRPC channels are an important but not singular aspect of these calcium entry mechanisms (Beech 2013 Circ J published on-line). They are expressed throughout the vasculature and probably in all cell types of the vasculature. These channels appear to have most significance as drivers of change when there is strain or insult in physiology or disease. Intriguingly, many, but not all, of the TRPC channel modulators are lipids or lipid-soluble substances; there are 10 known lipid modulators of the TRPC5 subtype and 9 of the TRPC6 subtype. These observations suggest that TRPC channels are lipid-sensing ion channels. Some of the lipid factors act directly, others indirectly (e.g. via lipid-sensing G-protein-coupled receptors). Our recent work has identified TRPC channels in perivascular and other adipocytes, which are key cell types in the control and storage of lipids and which play primary roles in cardiovascular health. The functional significance of these channels arises through negative regulation of adiponectin, a pivotal anti-inflammatory adipokine (Sukumar et al 2012 Circ Res 111, 191-200). The work identified dietary omega-3 fatty acids as inhibitors of these adipocyte TRPC channels and revealed the striking finding that the stimulatory effect of these fatty acids on adiponectin secretion is completely abrogated by in vivo genetic disruption of TRPC ion channel function. These and other recent findings will be discussed.