In the latest 2023 ESH guidelines for the treatment of hypertension, hypertension is defined as truly resistant when systolic blood pressure (BP) is ≥140 mmHg or diastolic BP is ≥90 mmHg at maximum recommended and tolerated doses of a three-drug combination, including a renin–angiotensin–system (RAS) blocker, a calcium channel blocker (CCB), and a thiazide/thiazide-like diuretic, and inadequate BP control has been confirmed by ambulatory measurements, and causes of pseudo-resistant hypertension and secondary hypertension have been excluded [5]. The gene discussed is REN; the disease is Hypertension.