To assess whether retinoschisin has the capacity to directly modulate MAP kinase signalling, we investigated the effect of recombinant retinoschisin on activation of the ERK pathway in two retinal model systems; the human retinoblastoma cell line Y‐79 and Rs1h−/Y murine retinal explants, both capable to bind extracellularly added retinoschisin due to an endogenous expression of the NA/K‐ATPase subunits α3 and β2. Here, MAPK1 is linked to retinoblastoma.