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In addition to mGPR17, several naturally occurring hGPR17L variants have distinct downstream second messenger signaling profiles when expressed in HEK293 cells [26]: human GPR17L-V96M has similar agonist-mediated inhibition of cAMP to that of hGPR17L-WT, but without the reversal of inhibition typically observed upon treatment with greater than 1 M MDL29,951 [26], and GPR17L-V96M shows impaired agonist-mediated calcium mobilization and -arrestin recruitment [26]

Ironically, these findings are coming to light in an era when their relevance is diminishing, with the advent of drugs (flozins and GLP1RAs) which can be safely used below GFR 30, and which also have evidence of clinical outcome benefits

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GLP-1 receptors are found in heart tissue and blood vessels, and the drugs appear to improve blood vessel function, reduce inflammation, and influence the buildup of plaque in arteries