The GENOMES UNCOUPLED 4 (GUN4) protein is found only in aerobic photosynthetic organisms. We investigated the role of GUN4 in metabolic activities of the Mg branch of the tetrapyrrole biosynthesis pathway and the plastid signal-mediated changes of nuclear gene expression inChlamydomonas reinhardtii. In light,gun4accumulates only 40% of the wild-type chlorophyll level. Light- or dark-growngun4mutant accumulates high levels of protoporphyrin IX (Proto), and displays increased sensitivity to moderate light intensities. Despite the photooxidative stress,gun4fails to downregulate mRNA levels of the tetrapyrrole biosynthesis and the photosynthesis-associated nuclear genes (PhANGs). In contrast, upon illumination, the Proto-accumulating and light-sensitivechlD–1mutant displays the expected downregulation of the same nuclear genes. AlthoughchlD–1and the wild type have similarGUN4transcript levels, the GUN4 protein inchlD–1is hardly detectable. Overexpression ofGUN4inchlD–1modifies the downregulation of nuclear gene expression, but also increases light tolerance. Therefore, GUN4 is proposed to function in ‘shielding’ Proto, and most likely MgProto, by reducing reactivity with O2. Furthermore, GUN4 seems to be involved in sensing elevated levels of these photoreactive tetrapyrrole intermediates, and contributing to 1O2-mediated retrograde signalling, originating from chlorophyll biosynthesis.