Adenylate kinases (AK) are widely existing in various organisms, which play critical roles in maintaining the normal content of nucleotides and regulation of energy metabolism in cells. Among AK family members, AK6, also known as human coilin-interacting nuclear ATPase protein (hCINAP), is an atypical adenylate kinase that possesses both activities of adenylate kinase and ATPase. We have been carried out long-term research on the structure, enzymatic activity and functions of this enzyme, and demonstrated that AK6/hCINAP plays critical roles in many biological processes, including gene transcription, ribosome quality control, embryonic development, senescence, cell metabolism, cell proliferation and apoptosis, DNA damage responses, inflammatory response, and tumor development. In this review, we summarize the structural features, biological roles and transcriptional regulators of AK6/hCINAP, which provides important insights into its activity and functions, and contributes to the screening of specific inhibitors of AK6/hCINAP and its application in clinical therapy in the future.