ARHGAP42 is a smooth muscle cell-selective GTPase-activating protein that primarily functions as a RhoA inhibitor to regulate blood pressure homeostasis 1. The protein contains GTPase activator activity and functions by suppressing RhoA-dependent vascular smooth muscle contractility 1. ARHGAP42 expression is controlled through multiple regulatory mechanisms: a blood pressure-associated SNP (rs604723) in an intronic enhancer promotes serum response factor binding to increase expression 1, while RBPJ and TEAD1 transcription factors cooperatively bind to regulate SMC-selective expression 2. Post-transcriptional regulation occurs through miR505-mediated degradation and long non-coding RNA AK124326-mediated transcriptional inhibition 2. Clinically, ARHGAP42 haploinsufficiency is associated with age-dependent hypertension 3, and a homozygous stop-gain variant causes childhood interstitial lung disease with systemic hypertension and enhanced RhoA signaling 4. The protein's role extends beyond vascular regulation, as elevated ARHGAP42 expression in nasopharyngeal carcinoma promotes cell migration and invasion through PI3K/Akt signaling 5. Additionally, ARHGAP42 expression levels contribute to a three-gene prognostic score for predicting clinical response to anti-PD-1 immunotherapy in renal cell carcinoma 6. These findings support ARHGAP42 as both a cardiovascular disease susceptibility gene and a potential oncogenic factor in certain cancers.