Gar1 is an essential small nucleolar ribonucleoprotein (RNP) protein. It contains two glycine-and arginine-rich GAR domains, localizes in the nucleolus, and is crucial for pre-rRNA processing in yeast, thus being involved in rRNA metabolism [2]. It is also a component of the H/ACA RNP complex, which is responsible for RNA-guided pseudouridylation, an important post-transcriptional RNA modification [4].

In the H/ACA RNP complex, Gar1 has multiple functions. It has a SUMO-interacting motif that mediates the interaction between dyskerin and itself, and this interaction is important for the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin's function as a telomerase-associated protein and an H/ACA ribonucleoprotein [1]. Gar1 also contributes to the RNA-guided and RNA-independent rRNA pseudouridylation activities of the archaeal Cbf5 protein. In vivo and in vitro, it is crucial for the RNA-guide-independent formation of Ψ2607 by Cbf5, and pseudouridylation at an orphan position also relies on the RNA-and Gar1-dependent activity of Cbf5 [5]. Additionally, Gar1 reduces the catalytic barrier in H/ACA RNA-guided pseudouridylation by affecting the activation entropy, helps place the target uridine correctly for the catalytic reaction, and is involved in product release [3]. In archaea, it increases the catalytic activity of Cbf5 in pseudouridylating tRNA by enhancing Cbf5's affinity for tRNA and directly increasing Cbf5's catalytic activity, though it is not involved in product release after tRNA modification [6].

In conclusion, Gar1 is a key protein in the nucleolus, playing essential roles in rRNA processing and RNA pseudouridylation. Its functions in these processes are vital for normal cellular activities. Although no KO/CKO mouse models are directly mentioned in the references, the in-vitro and in-vivo studies on yeast and archaea provide valuable insights into its biological functions, which may potentially be relevant to understanding similar processes in mammals and related disease mechanisms.