The γ subunit has been characterized as a fine-tuning modulator of the Na/K-ATPase expressed in kidney tissues. This small single transmembrane domain protein interacts with the alpha subunit of Na/K-ATPase to increase affinity for ATP and decrease affinity for Na allowing medullary cells to continue pump activity under reduced cellular ATP levels. The γ subunit is undetectable in kidney cell cultures grown under isotonic conditions and expression is induced with acute or chronic exposure to hypertonicity. The γ subunit demonstrates remarkable regulatory complexity including induction by chloride ions rather than sodium, the differential expression of at least 2 isoforms, involvement of separate MAP kinase signaling pathways for transcription (JNK) and translation (PI3K) as well as cell type regulation of expression. Mutation in the transmembrane domain of the γ subunit has been implicated in cases of primary hypomagnesemia. Alternative roles have been established for the γ subunit in embryonic development and quite possibly additional functions in cell signaling as yet unrecognized may be possible.