Implications of ADP ‐Ribosylation Factor‐Like Protein 4C ( ARL4C ) in Human Neoplasia With Special Emphasis on Ameloblastoma: A Scoping Review

BACKGROUND: ADP-ribosylation factor-like protein 4C (ARL4C), a member of the ARF small GTP-binding protein subfamily, has emerged from its role as an epithelial growth regulator to become a central molecule in cancer biology. This scoping review was conducted according to the PRISMA-ScR framework, systematically maps literature from PubMed, Scopus and Web of Science up to December 2024 to synthesise evidence on ARL4C's regulatory mechanisms and its implications in tumourigenesis and relevance to ameloblastoma. FINDINGS: Originally recognised for its role in tissue morphogenesis, ARL4C is now known to drive cancer cell proliferation, migration and invasion when dysregulated. Its expression is modulated by major signalling cascades including Wnt/MAPK, PI3K/AKT and TGF-β, as well as epigenetic factors. While primarily acting as an oncogenic driver, ARL4C exhibits context-dependent roles, occasionally functioning as a tumour suppressor. In ameloblastoma, a locally aggressive odontogenic tumour, ARL4C expression correlates with invasion and bone resorption. Notably, this influence appears independent of BRAF mutation status, suggesting a unique pathological role in this setting. CONCLUSION: ARL4C stands at the intersection of fundamental cell biology and clinical oncology. It holds promise as a biomarker for prognosis and recurrence and as a potential therapeutic target. However, its dual nature highlights the complexity of cancer signalling networks. Future research involving larger patient cohorts is essential to validate ARL4C's utility in precision oncology, particularly for the management of ameloblastoma.