Background: R-Spondin-1 is a protein involved in cellular signaling pathways that play crucial roles in skin homeostasis, development, and regeneration. Dysregulation of R-Spondin-1 levels has been observed in various dermatological conditions, including inflammatory disorders, skin cancers, and hair disorders. Understanding the role of R-Spondin-1 in these conditions may provide insights into their pathogenesis and potential therapeutic targets. Objectives: This article aims to demonstrate the role of R-Spondin-1 protein in different dermatosis conditions. It aims to examine its physiological function, explore its dysregulation mechanisms, review its diagnostic potential and also investigate therapeutic implications. Conclusions: R-Spondin-1 emerges as a promising molecule with multifaceted roles in dermatological conditions. Its altered expression levels and signaling pathways provide diagnostic and prognostic insights in skin disorders, such as psoriasis, atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, and melanoma. Furthermore, targeting R-Spondin-1 signaling holds therapeutic potential for the development of novel interventions in these dermatosesBackground: R-Spondin-1 is a protein involved in cellular signaling pathways that play crucial roles in skin homeostasis, development, and regeneration. Dysregulation of R-Spondin-1 levels has been observed in various dermatological conditions, including inflammatory disorders, skin cancers, and hair disorders. Understanding the role of R-Spondin-1 in these conditions may provide insights into their pathogenesis and potential therapeutic targets. Objectives: This article aims to demonstrate the role of R-Spondin-1 protein in different dermatosis conditions. It aims to examine its physiological function, explore its dysregulation mechanisms, review its diagnostic potential and also investigate therapeutic implications. Conclusions: R-Spondin-1 emerges as a promising molecule with multifaceted roles in dermatological conditions. Its altered expression levels and signaling pathways provide diagnostic and prognostic insights in skin disorders, such as psoriasis, atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, and melanoma and other disseise. Furthermore, targeting R-Spondin-1 signaling holds therapeutic potential for the development of novel interventions in these dermatoses.