Who is who within the universe of TREM-like transcripts (TREML)?

The Triggering Receptor Expressed on Myeloid Cells (TREM) family of receptors plays a crucial role in the immune response across various species. Particularly, TREM-1 and TREM-2 have been extensively studied, both in terms of their applications and their expression sites and signaling pathways. However, the same is not observed for the other family members collectively known as TREM-like-transcripts (TREML). The TREML family consists of eight receptors, with TREML1–5 identified in humans and mice, TREML-6 exclusive found in mice, TREML-7 in dogs and horses, and TREML-8 in rabbits and opossums. Despite the limited data available on the TREML members, they have been implicated in different immune and non-immune activities, which have been proposed to display both pro and anti-inflammatory activities, and to influence fundamental biological processes such as coagulation, bone and neurological development. In this review, we have compiled available information regarding the already discovered members of the family and provided foundational framework for understanding the function, localization, and therapeutic potential of all TREML members. Additionally, we hope that this review may shed light on this family of receptors, whose underlying mechanisms are still awaiting elucidation, while emphasizing the need for future studies to explore their functions and potential therapeutic application.