The authors make the case that the thalamic TIP39 peptide is crucial for expressing some behaviors. The review is timely since there are few writings on the subject. It covers the current knowledge and allows for further research to approach the gaps in the field. This review starts with a general overview of the history of the discovery; its pharmacology; anatomy; the tools used to interrogate it; and a description of different behaviors in which it participates. Some minor observations that might be of utility are the following:

Page 3, second paragraph. Should it be?: "the only known endogenous ligand for the PTH2R, the three peptides do have a similar three-dimensional structure."

Page 4, The section on anatomical distribution states that Tip39 is expressed in only three brain areas. It should say that neuronal somas expressing TIP39 have been identified in just three areas.

In the text, there is a reference to Figure 1:

Fig. 1 shows some TIP39 fibers in MPoA (the greek letter is missing in the figure legend).

Fig. 2: Can also be referenced here

For ease of reading, in both figures, it might be good to indicate using green and red letters within the photos, which are the antigens.

In the last sentence of the anatomy section, It might sound less categorical to say: "No other known peptides have been identified in neurons of the MPL."

Section on nociception:

Missing reference to support the argument of older nociceptive pathways involved in affective vs. younger pathways involved in sensory aspects of pain processing

Missing reference for the last two sentences of this section

The section on fear responses:

Concerning the last sentence of the first paragraph, I see no apparent connection between the mentioned study on the adrenergic system participation in fear and TIP-39.

In the fourth line before the end of the second paragraph, do you want to say PTH2R-expressing neurons instead of PTH2R-expression neurons?

The section on anti-depressive actions of TIP39

Some references have weird numeration, i.e., 988, 1377

The section on maternal behaviors

Second paragraph. The statement " The preoptic area of the hypothalamus is the brain area most critical for maternal behavior in rodents."

Suggestion:
A figure representing the current knowledge of the TIP39 producing neurons and the receptor localization within the rat brain would be helpful to give a clear message. A suggestion could be to update the Fig 9 of the 2010 Prog. Neurobiology review, to include the areas known to have receptors, the three thalamic areas where somas have been reported, and possible circuits. Current figures 1 and 2 can be some insets to show the fibers in some of those areas.