Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy

Efferocytosis, the process of apoptotic cell clearance, is a fundamental biological mechanism for maintaining tissue homeostasis. However, its role in disease pathogenesis is often oversimplified, neglecting a critical knowledge gap: how the single process could drive opposing pathological outcomes. This review provides a comprehensive analysis centered on the functional duality of efferocytosis. By synthesizing evidence across a spectrum of human pathologies-from atherosclerosis and neurodegeneration to cancer-we establish a core paradigm: impaired efferocytosis is a central pathogenic driver in chronic inflammatory and autoimmune diseases, leading to unresolved inflammation. Conversely, the hijacking of efferocytosis by tumors fosters an immunosuppressive microenvironment, facilitating immune evasion. This dichotomy presents a significant therapeutic conundrum, as enhancing efferocytosis benefits inflammatory conditions but exacerbates cancer. By dissecting these context-dependent mechanisms, we argue that the future of efferocytosis-based medicine hinges on developing targeted, disease-specific strategies to safely harness this powerful biological process.