The ubiquitin‐like modifier FAT10 targets proteins for degradation by the proteasome, a process accelerated by the UBL‐UBA domain protein NEDD8 ultimate buster 1‐long. Here, we show that FAT10‐mediated degradation occurs independently of poly‐ubiquitylation as purified 26S proteasome readily degraded FAT10‐dihydrofolate reductase (DHFR) but not ubiquitin‐DHFR in vitro. Interestingly, the 26S proteasome could only degrade FAT10‐DHFR when NUB1L was present. Knock‐down of NUB1L attenuated the degradation of FAT10‐DHFR in intact cells suggesting that NUB1L determines the degradation rate of FAT10‐linked proteins. In conclusion, our data establish FAT10 as a ubiquitin‐independent but NUB1L‐dependent targeting signal for proteasomal degradation.