Leucine-rich repeats (LRRs) are versatile motifs present in more than 6000 proteins throughout the phylogenetic kingdom. Tandem LRRs generate a characteristic horseshoe with a diverse range of functions. Fulfilling a key role in the innate immune system, LRRs form the TLR and NOD-like receptor (NLR) pathogen-recognition domain. Host–pathogen interactions mediated by LRRs drive those involved in ligand recognition to become distinct from their consensus motif. Most LRRs range between 21 and 30 residues; however, large insertions in certain TLRs can generate repeats of over 60 amino acids. LRR variability makes them ideal for species-specific mediation of host-pathogen interactions. Teleost TLRs show large insertions, making cross-species alignments difficult without prior demarcation of their LRR motifs. We present LRRfinder2.0, a webserver for LRR prediction. LRRfinder2.0 utilizes scoring matrices comprising more than 60,000 LRR motifs from more than 200 species. The underlying TLR database tLRRdb contains more than 3500 manually annotated sequences, augmenting identification of irregular LRR motifs.