ABSTRACT Radial glia‐like cells (RGLCs) are recognized as cells with morphological and molecular similarities to embryonic radial glia but present in the nervous system of adult organisms. They are well known for playing key roles in neurogenesis and regeneration. The characterization of RGLCs in invertebrates has faced serious challenges due to interspecies limitations in identifying markers common to the vertebrate radial glia or RGLCs. This study investigates RGLCs in the echinoderm Holothuria glaberrima , combining transcriptomics, immunofluorescence, and advanced RNA visualization techniques (hybridization chain reaction fluorescence in situ hybridization [HCR‐FISH]). Our results reveal the expression and localization of nine RGLC markers in the echinoderm central nervous system. These markers ( GS , PAX6 , SOXB1 , Prominin, GLAST , SCO‐spondin, Netrin, EAAT2 , UNC5C ) have been previously associated with vertebrate glial cells and/or their neurogenetic functions. Additionally, using an in vitro injury model, we tested the RGLC ability to respond to injury. This showed significant changes in the expression of key markers such as PAX6 and Prominin, indicating the RGLC ability to react to injury. Our work provides insights into the phylogenetic relationships between vertebrate and invertebrate glial cells. This work advances our understanding of echinoderm RGLCs, challenging traditional views of glial cell homology and expanding the framework for studying neuroregenerative processes in nontraditional organisms.