Lipopolysaccharide-induced tumor necrosis factor-α (LITAF) is a membrane protein that is highly dependent on correct location to exert transcription factor activity and protein quality control. In humans, LITAF, PIG7 (p53-inducible gene 7), and SIMPLE (small integral membrane protein of the lysosome/late endosome) refer to the same gene, which acts as a tumor suppressor. Several studies have shown that the transcription factor activity and nuclear translocation of LITAF protein are critical for the induction of several immune cells via classical pathways. In plants, LITAF protein corresponds to the plasma membrane protein AtGILP (Arabidopsis thaliana GSH-induced LITAF domain protein). The conservation of LITAF proteins across species and their putative role is still unclear. In this study, we investigate the LITAF-containing proteins, which we call GILP proteins, in Viridiplantae. We identified a total of 59 genes in 46 species, whose gene copies range from one to three. Phylogenetic analysis showed that multiple copies were originated via block duplication posteriorly to monocot and eudicot separation. Analysis of the LITAF domain of GILP proteins allowed the identification of a putative domain signature in Viridiplantae, containing a CXXCX41HXCPXC motif. The subcellular location for the majority of GILP proteins was predicted to be in the plasma membrane, based on a transmembrane domain positioned within the LITAF domain. In silico analysis showed that the GILP genes are neither tissue-specific nor ubiquitously expressed, being responsive to stress conditions. Finally, investigation of the GILP protein network resulted in the identification of genes whose families are known to be involved with biotic and/or abiotic stress responses. Together, the expression modulation of GILP genes associated with their plasma membrane location suggests that they could act in the signaling of biotic/abiotic stress response in plants.