NDRG1

NDRG1, or N-myc downstream-regulated gene 1, is a protein-coding gene in humans and a member of the NDRG family. The encoded protein is a cytoplasmic phosphoprotein expressed in many tissues, with notable abundance in the nervous system and skeletal muscle. NDRG1 is implicated in cellular differentiation, development, and responses to cellular stress, and it is involved in maintenance of cytoskeletal integrity and cell–cell interactions.

The gene's name reflects its initial identification as a downstream target of the N-Myc family of transcription factors; subsequent studies show that NDRG1 integrates signals from multiple pathways. Expression is induced by hypoxia and iron deprivation and can be regulated by p53 in response to DNA damage. Phosphorylation by SGK1 modulates NDRG1 localization and function and links its activity to signaling pathways governing cell survival and metabolism.

In cancer biology, NDRG1 is frequently described as a metastasis suppressor that can inhibit tumor cell invasion and dissemination, although its role is context dependent and may vary by tissue type and microenvironment.

Clinically, mutations in NDRG1 cause Charcot–Marie–Tooth disease type 4D, an autosomal recessive demyelinating neuropathy characterized by distal weakness and sensory impairment. The disease highlights the importance of NDRG1 in Schwann cell biology and myelin maintenance. NDRG1 continues to be studied as a potential biomarker and therapeutic target in cancer and neurodegenerative diseases.