This disclosure relates to variable lymphocyte receptors (VLRs) modifications such as humanized sequences and polypeptides comprising such sequences that specifically bind a target molecule and uses related thereto. In certain embodiments, the disclosure relates to recombinant polypeptide VLRs disclosed herein and variants thereof. In certain embodiments, this disclosure relates to treating or preventing a disease or condition comprising administering an effective amount of a recombinant polypeptide or variant disclosed herein to a subject in need thereof.