The reported functions of TMEFF2 span across a wide range of physiological and pathological spectra, ranging from corticotropin release hormone (CRH) stimulation in the anterior pituitary gland and providing neuroprotection by binding the amyloid β protein derivatives in Alzheimer’s disease on one hand to triggering the JAK-STAT pathway in colorectal cancer and modulating one-carbon metabolism in prostate tissue on the other. This evidence concerns the gene TMEFF2 and early-onset autosomal dominant Alzheimer disease.