Groundbreaking work expands understanding of cardiovascular and metabolic diseases. The adipokine hypothesis links alterations in internal fat biology to heart failure with preserved ejection fraction (HFpEF). Empagliflozin shows notable cardiovascular and renal benefits in obese patients. Additionally, the STUB1-TPIT axis regulates ACTH secretion in Cushing’s disease, opening new therapeutic avenues. Novel pan-EphB inhibitors demonstrate potential in treating metabolic syndrome, underscoring the value of signaling pathways as drug targets.