GDF11 is a secreted signaling molecule that regulates developmental patterning and cellular homeostasis through activin receptor signaling. During development, GDF11 is required for proper vertebral patterning and orofacial development 1 and enables posterior neural crest patterning during enteric nervous system formation 2. GDF11 signals through activin type II receptors (ACVR2A/2B) and type I receptors (ACVR1B/1C/TGFBR1), leading to SMAD2/3 phosphorylation 3. In adult tissues, GDF11 functions as a protective factor against aging and degeneration. In the brain, GDF11 is predominantly expressed in excitatory neurons where it acts as a brake on neuronal senescence by repressing p21 expression; GDF11 deletion induces senescence, hyperexcitability, and shortened lifespan 4. In cartilage, GDF11 suppresses TNF-α-induced inflammation and cartilage degeneration by inhibiting NLRP3 inflammasome activation, protecting against osteoarthritis 5. GDF11 also regulates cardiac function; increased activin/GDF11 signaling impairs cardiac function through proteasome-dependent degradation pathways 6. Clinically, GDF11 is therapeutically relevant in multiple disease contexts. Elevated GDF11 contributes to pulmonary hypertension pathogenesis, and blocking GDF11 signaling with ACTRIIA-Fc improves hemodynamics and prevents vascular remodeling 7. In skeletal muscle, GDF11 negatively regulates mass; blocking GDF11 and myostatin signaling via ActRII inhibition promotes muscle hypertrophy and prevents cachexia 89.