Understanding the processes that give rise to genomic variability in extant species is an active area of research within evolutionary biology. With the availability of whole genome sequences, it is possible to quantify different forms of variability such as variation in gene copy number, which has been described as an important source of genetic variability and in consequence of phenotypic variability. Most of the research on this topic has been focused on understanding the biological significance of gene duplication, and less attention has been given to the evolutionary role of gene loss. Gremlin 2 is a member of the DAN gene family and plays a significant role in tooth development by blocking the ligand-signaling pathway of BMP2 and BMP4. The goal of this study was to investigate the evolutionary history of gremlin 2 in cetartiodactyl mammals, a group that possesses highly divergent teeth morphology. Results from our analyses indicate that gremlin 2 has experienced a mixture of gene loss, gene duplication, and rate acceleration. Although the last common ancestor of cetartiodactyls possessed a single gene copy, pigs and camels are the only cetartiodactyl groups that have retained gremlin 2. According to the phyletic distribution of this gene and synteny analyses, we propose that gremlin 2 was lost in the common ancestor of ruminants and cetaceans between 56.3 and 63.5 million years ago as a product of a chromosomal rearrangement. Our analyses also indicate that the rate of evolution of gremlin 2 has been accelerated in the two groups that have retained this gene. Additionally, the lack of this gene could explain the high diversity of teeth among cetartiodactyl mammals; specifically, the presence of this gene could act as a biological constraint. Thus, our results support the notions that gene loss is a way to increase phenotypic diversity and that gremlin 2 is a dispensable gene, at least in cetartiodactyl mammals.