Proto-oncogene tyrosine-protein kinase receptor RET, activates the MAPK pathway for cell proliferation and the PI3K/AKT pathway for cell survival. Certain inherited mutations in the RET proto-oncogene predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes including MEN 2A and 2B, and familial medullary thyroid carcinoma. Somatic mutations in RET are rare in squamous cell carcinoma of the lung and are found in 2-3% of cases. RET E623K lies within the extracellular domain of the RET protein, but has not been characterized and therefore its effect on RET protein function is unknown. RET E623K has been reported as a benign germline mutation in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/24906/). These results should be interpreted in the clinical context.