Protozoan parasites are known for their remarkable capacity to persist within the bodies of vertebrate hosts, which frequently results in prolonged infections and the recurrence of diseases. Understanding the molecular mechanisms that underlie the event of persistence is of paramount significance to develop innovative therapeutic approaches, given that these pathways still need to be thoroughly elucidated. The present article provides a comprehensive overview of the latest developments in the investigation of protozoan persistence in vertebrate hosts. The focus is primarily on the function of persisters, their formation within the host, and the specific molecular interactions between host and parasite while they persist. Additionally, we examine the metabolomic, transcriptional, and translational changes that protozoan parasites undergo during persistence within vertebrate hosts, focusing on major parasites such as Plasmodium spp., Trypanosoma spp., Leishmania spp., and Toxoplasma spp. Key findings of our study suggest that protozoan parasites deploy several molecular and physiological strategies to evade the host immune surveillance and sustain their persistence. Furthermore, some parasites undergo stage differentiation, enabling them to acclimate to varying host environments and immune challenges. More often, stressors such as drug exposure were demonstrated to impact the formation of protozoan persisters significantly. Understanding the molecular mechanisms regulating the persistence of protozoan parasites in vertebrate hosts can reinvigorate our current insights into host–parasite interactions and facilitate the development of more efficacious disease therapeutics.

Ribosomes, in general, are viewed as constitutive macromolecular machines where protein synthesis takes place; however, this view has been recently challenged, supporting the hypothesis of ribosome specialization and opening a completely new field of research. Recent studies have demonstrated that ribosomes are heterogenous in their nature and can provide another layer of gene expression control by regulating translation. Heterogeneities in ribosomal RNA and ribosomal proteins that compose them favor the selective translation of different sub-pools of mRNAs and functional specialization. In recent years, the heterogeneity and specialization of ribosomes have been widely reported in different eukaryotic study models; however, few reports on this topic have been made on protozoa and even less on protozoa parasites of medical importance. This review analyzes heterogeneities of ribosomes in protozoa parasites highlighting the specialization in their functions and their importance in parasitism, in the transition between stages in their life cycle, in the change of host and in response to environmental conditions.