The Cashmere goat is an excellent local goat breed in Gansu Province of China, and it is expected to improve cashmere production and cashmere quality through selection and breeding to enhance its commercial value. Keratin-associated proteins (KAPs) play an important role in maintaining wool structure. The gene encoding the keratin-associated protein 22-2 (KAP22-2) gene has been identified in selected species other than goats, such as humans, mice, and sheep. In this study, the sequence of the sheep KAP22-2 gene (KRTAP22-2) was aligned into the goat genome, and the sequence with the highest homology was assumed to be the goat KRTAP22-2 sequence and used to design primers to amplify the goat gene sequence. A total of 356 Longdong Cashmere goats (Gansu Province, China) were used for screening of genetic variants. Four specific bands were detected by polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analysis, and they formed a total of six band types individually or in combination. Four alleles were identified by DNA sequencing of PCR amplification products. A total of four single nucleotide polymorphic sites (SNPs) were detected in the four sequenced KRTAP22-2 alleles. Two of them are in the 5’UTR region and the other two are in the coding region, and the variants in the coding region are all non-synonymous mutations. In addition, there was a 6 bp length variation in allele C. The gene was expressed in the cortical layer of primary and secondary hair follicles, the inner root sheath, as well as hair papillae and hair maternal cells in goats. The results of the correlation analysis between genotypes and cashmere traits showed that after excluding genotypes with a gene frequency of less than 5%, the mean fiber diameter (MFD) of cashmere was significantly higher in the AB genotype than in the AA and AC genotypes. That is, the KRTAP22-2 gene variants are associated with mean fiber diameter in cashmere. The above results suggest that the goat KRTAP22-2 variant can be utilized as a molecular marker candidate gene for cashmere traits.