Compelling human genetic validation for GPR65 as a therapeutic target comes from The Cancer Genome Atlas (TCGA) analyses performed by Pathios [Supplemental data], demonstrating that cancer patients homozygous for the hypomorphic I231L coding variant (rs3742704) (which exhibits significantly reduced GPR65 signalling capacity) display markedly improved overall survival across multiple solid tumour types compared to patients with wild-type GPR65 [Figure 3] [123]. The gene discussed is GPR65; the disease is cancer.