Coelomic epithelium (CE), or coelothelium, is a mesodermal-derived tissue lining coelomic cavities and enveloping inner organs in all coelomates, including vertebrates, where it forms both peritoneum and pericardium, as well as pleura, in mammals. Due to its histogenetic potential, CE is considered a key-tissue characterized by unique features. At present, in adult echinoderms, CE is supposed to play fundamental key roles acting as: 1) source of stem/multipotent cells (undifferentiated coelomocytes), particularly during regenerative phenomena (Candia Carnevali et al., 2009; Candia Carnevali and Burighel, 2010; Hernroth et al., 2010; García-Arrarás et al., 2011). 2) haematopoietic tissue, being the direct source of circulating elements (differentiated coelomocytes) including immune cells, indispensable elements during the first repair events of clotting and defence against pathogens (Boassche and Jangoux, 1976; Munoz-Chapuli et al., 2005; Pinsino et al., 2007). Despite these indications, the histological approach alone, microscopic or ultrastructural, is not sufficient to fully attribute a haematopoietic role to the CE and even the presumptive production/release process of stem/pluripotent cells from coelothelium during regeneration need to be confirmed as well. As a matter of fact, it is still unclear if the intense proliferation detectable in regenerating CE is functional to the production of wandering coelomocytes necessary to restore the post-traumatic fluid loss or rather to produce truly regeneration-competent cells used as building blocks of the regenerating tissues. In order to overcome some of these issues and deeply understand the complex physiological role of this epithelial tissue in echinoderm biology, it is important to integrate morphological evidences with detailed molecular data. In particular, proteomics is becoming a powerful tool to deepen the problem of cell and tissue functions during both tissue homeostasis and regeneration by depicting the existing protein activities involved in the regrowth processes. However, proteomics investigations focussed on echinoderm CE are quite limited. Specific molecular information are due to the works by Gabre and co-workers (2015) and by Kim and co-workers (2018), which are addressed to the characterization of CE transcriptome from the clonal starfish Coscinasterias muricata and the blue bat starfish Patiria pectinifera, respectively. The analysis of the biological processes associated to the transcripts identified in these studies suggests the involvement of CE in the development of anatomical units. More recently the CE proteome of the common starfish Asterias rubens was also published (Sharlaimova et al., 2021). Despite these evidences, there is a great lack of integrated multidisciplinary studies that can contribute to unravel the complex roles exerted by this tissue both in regeneration and other physiological processes. In order to partially unravel this gap, the present work is addressed to analyse the CE of the starfish Marthasterias glacialis in both standard physiological (homeostatic) and regenerating conditions, by combining histological/ultrastructural analyses with appropriate proteomics approaches, the former to provide a detailed cell and tissue perspective, the latter to contribute a base-line molecular view of CE multifunctional implications. This integrated approach can significantly help to shed new light into the intriguing role of this apparently simple but fundamental tissue.