Hereditary angioedema is a rare and disabling disorder caused by mutations in the SERPING1 gene. These mutations ultimately lead to deficient or dysfunctional C1 esterase inhibitor and unregulated activation of the kallikrein-kinin system. This review discusses the current epidemiology, etiology, and pathophysiology of the disorder and highlights how advances in our understanding have reframed diagnostic and therapeutic strategies. We further delineate the roles of classical, alternative, and lectin complement pathways in hereditary angioedema's pathophysiology and discuss C1 esterase inhibitor within the broader serpin family context. We discuss implications for clinical practice, including diagnostic workups, genetic considerations, and targeted therapies that modulate the bradykinin pathway, aiming to shorten diagnostic timelines and optimize patient outcomes.
