FSTL5 (follistatin-like 5) encodes a secretory glycoprotein that functions as a modulator of developmental and disease-relevant signaling pathways. Primary Function: FSTL5 is expressed in restricted developmental contexts, including embryonic hindlimb cartilage condensations and postnatal growth plate prehypertrophic chondrocytes 1, as well as in specific adult brain regions including the olfactory system and hippocampus 2. Mechanism: FSTL5 regulates transforming growth factor beta and bone morphogenetic protein signaling 1 and acts as a suppressor of Wnt/β-catenin signaling in hepatocellular carcinoma 3. In HCC, miR-1246 targets FSTL5 to promote cancer progression via ERK/p38 MAPK pathway activation 4. Disease Relevance: FSTL5 variants are significantly associated with isolated clubfoot (talipes equinovarus) development 1, with potential sexually dimorphic effects on skeletal growth in males 1. FSTL5 is downregulated in hepatocellular carcinoma, correlating with increased tumor size, TNM stage, and poor prognosis 3. Additionally, FSTL5 loci associate with early-onset gout 5 and tuberculosis susceptibility 6. Clinical Significance: FSTL5 expression and genetic variants may serve as prognostic biomarkers in HCC and other malignancies, with therapeutic potential in modulating aberrant signaling pathways.