CIART (circadian associated repressor of transcription) is a transcriptional repressor that forms a core negative regulatory component of the circadian clock independent of CRY1, CRY2, and BHLHE41 1. CIART represses CLOCK-BMAL1 heterodimer activity through histone deacetylase-dependent mechanisms, disrupting BMAL1-CREBBP interaction and reducing histone acetylation of circadian target genes 1. CIART rhythmically binds E-box elements on circadian gene promoters with antiphasic oscillation to BMAL1, and interacts with the glucocorticoid receptor to modulate glucocorticoid signaling 1. Disease relevance is emerging across multiple conditions. CIART expression is dysregulated in bipolar disorder, where imbalanced activation/repression within the circadian system distinguishes affected individuals from healthy controls 1. CIART functions as a key host factor controlling SARS-CoV-2 infection across lung and cardiac organoids through NR4A1 regulation and Retinoid X Receptor pathway modulation 2. CIART dysregulation is implicated in hypertensive complications 3, aging-related lens pathology 4, opioid-induced hyperalgesia 5, leukemia microenvironment remodeling 6, and sex hormone-dependent cardiac hypertrophy 7. ClockΔ19 studies link CIART disruption to hippocampal abnormalities resembling bipolar disorder pathology 8. Clinically, CIART represents a potential therapeutic target for COVID-19, circadian rhythm disorders, and hypertension management through circadian pathway modulation.