Chordin-like 1 (CHRDL1)

Chordin-like 1 (CHRDL1) is a secreted glycoprotein and a member of the Chordin family that functions primarily as a high-affinity antagonist of bone morphogenetic proteins (BMPs), particularly BMP4 [1, 12]. By binding to BMPs in the extracellular space, CHRDL1 prevents their interaction with cell surface receptors, thereby modulating key signaling pathways involved in embryonic development, organogenesis, and tissue homeostasis [4, 11]. It plays a critical role in the development of the anterior segment of the eye, and mutations in the CHRDL1 gene are the primary cause of X-linked megalocornea [3, 6]. Beyond its developmental roles, CHRDL1 is increasingly recognized as a potent tumor suppressor in various malignancies, including lung adenocarcinoma and breast cancer, where its downregulation is associated with increased metastasis, epithelial-to-mesenchymal transition (EMT), and poor patient prognosis [2, 5, 7]. CHRDL1 also influences the immune microenvironment, where higher expression levels correlate with increased infiltration of beneficial immune cells like CD8+ T lymphocytes [2, 15]. Recent research highlights its potential therapeutic application in regenerative medicine, specifically for treating myocardial infarction by limiting cardiac fibrosis and promoting tissue repair [10]. While no drugs targeting CHRDL1 are currently approved, experimental approaches such as CHRDL1 mRNA therapy and recombinant protein administration are being explored in preclinical models [10, 12].

Other names

Chordin-like protein 1Neuralin-1Neurogenesin-1VentroptinMegalocornea 1, X-linkedMGC1MGCNVOPTCHLNRLN1

Antagonism of BMP4 signaling through direct extracellular binding to prevent receptor activation; inhibition of TGF-beta signaling to prevent myofibroblast differentiation; modulation of MAPK signaling pathways (ERK, p38, JNK) to inhibit tumor metastasis [3, 7, 10, 11].