NDRG4 (N-Myc downstream regulated gene 4) is a cytoplasmic protein with tissue-specific expression primarily in brain and heart, where it plays critical roles in cellular homeostasis and tumor suppression 1. The gene encodes three alternatively spliced isoforms (NDRG4-B, NDRG4-B(var), and NDRG4-H) with brain-specific and heart-specific expression patterns 1. NDRG4 functions as a tumor suppressor gene, particularly in colorectal cancer, where its expression is frequently silenced through promoter hypermethylation in 70-86% of tumors compared to only 4% in normal colon mucosa 2. Functionally, NDRG4 overexpression suppresses colony formation, cell proliferation, and invasion in colorectal cancer cell lines 2. In meningiomas, NDRG4 is paradoxically overexpressed and promotes cell survival, invasion, migration, and angiogenesis, suggesting context-dependent functions 3. The clinical significance of NDRG4 lies in its utility as a diagnostic biomarker for colorectal cancer screening. NDRG4 promoter methylation analysis in stool DNA demonstrates 53-61% sensitivity and 93-100% specificity for colorectal cancer detection 2. This biomarker is now incorporated into FDA-approved multitarget stool DNA tests for colorectal cancer screening, showing superior detection rates compared to traditional fecal immunochemical tests 4.