Background/Objectives: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), originally developed for Type II Diabetes, has become popular for weight loss due to its ability to suppress appetite and promote fat loss. Although semaglutide’s metabolic benefits are well established, many patients have also reported unintended facial changes including facial fat atrophy, skin laxity, and an aged appearance, collectively known as “Ozempic face.” Methods: To better understand these dermatological effects, a narrative review was conducted using PubMed and Google Scholar to identify relevant peer-reviewed literature published between 2010 and 2025. Search terms included “semaglutide,” “GLP-1 receptor agonists,” “Ozempic face,” and “facial fat loss.” Peer-reviewed clinical studies, reviews, and relevant commentary were included; articles not written in English or unrelated to weight-loss aesthetic outcomes were excluded. Results: Weight loss induced by semaglutide is distinctly characterized by rapid, disproportionate depletion of sensitive facial fat compartments such as the malar, temporal, and buccal regions. Preliminary findings also suggest that GLP-1RAs may impact dermal white adipose tissue, affecting collagen production and elastin structure. Findings highlight both the biological mechanisms underlying facial aging in semaglutide users and the current lack of research-based strategies to prevent or treat these changes. Conclusions: Although aesthetic interventions such as dermal fillers and energy-based treatments may help restore volume and contour, more research is needed to characterize long-term effects and develop objective clinical guidelines. Increased counseling and awareness regarding GLP-1RA-induced facial changes should be integrated into patient care, especially as these agents continue to expand in popularity.

Background: Receptor Expressed in Lymphoid Tissues (RELT) is a TNFRSF member that has two paralogs, RELL1 and RELL2; the three proteins are collectively referred to as RELT family members (RELTfms). Methods: We sought to evaluate RELT expression in cancerous cells by using real-time PCR, western blotting, flow cytometry, and immunohistochemistry (IHC). The mechanism of RELT-induced cell death was assessed by western blotting, flow cytometry, luciferase assays, and morphology staining. RELT localization was detected through immunofluorescence and western blotting, and co-immunoprecipitation was used to test whether a mutated RELT interacts with the OXSR1 kinase. Results: RELT and RELL1 protein expression was significantly elevated in cell lines representing breast and lung cancer, whereas RELL2 protein expression was relatively consistent across different cell lines. The surface expression of RELT was highest in monocytes. IHC staining revealed increased RELT expression in malignant breast cancer biopsies compared to patient-matched benign tissue. RELTfm overexpression induced death in MDA-MB-231 (231) breast cancer cells, accompanied by increased phosphatidylserine externalization and Caspase-3/7 activation. The co-transfection of plasmids predicted to block the phosphorylation of RELT by the OXSR1 kinase did not abrogate RELT-induced apoptosis, indicating that the activation of p38 by RELT through the OXSR1 kinase is not required for RELT-induced cell death. Interestingly, nuclear localization of RELT was detected in 231 and HEK-293 cells. Conclusions: These results demonstrate that RELT induces death in breast cancer cells through an apoptotic pathway that does not require OXSR1 phosphorylation and that RELT possesses the ability to translocate to the nucleus, a novel finding that warrants further investigation.