GREM2 is a secreted BMP antagonist that modulates bone morphogenetic protein signaling across multiple biological contexts. Functionally, GREM2 inhibits BMP2 and BMP4 activity in a dose-dependent manner through direct binding, with independent heparin/heparan sulfate-binding epitopes that do not overlap with its BMP-antagonistic function 1. During fetal ovarian development, GREM2 fine-tunes BMP pathway intensity to regulate gene expression in somatic cells, contributing to primordial follicle formation 2. In adipose tissue, GREM2 suppresses visceral preadipocyte browning by antagonizing BMP4/7-BMPR2 signaling, with elevated serum GREM2 levels positively associated with visceral fat volume in obese individuals 3. In breast cancer, GREM2 functions as a tumor suppressor: low GREM2 expression correlates with poor prognosis and promoter hypermethylation, while GREM2 overexpression suppresses proliferation by repressing ID1 expression downstream of BMP signaling 4. In bone homeostasis, miR-671-3p targeting of GREM2 activates BMP2/SMAD signaling to promote osteogenic differentiation and prevent postmenopausal osteoporosis 5. Clinically, GREM2 mutations cause tooth agenesis with variable expressivity and incomplete penetrance, affecting tooth development through disrupted BMP antagonism 6, with functional variants altering gene transcription and affecting MSX1 expression 7.