This is a multicenter, open-label study to evaluate the safety, tolerability, and efficacy of 4% QRX003 lotion applied twice daily (BID) for 12 weeks to Netherton syndrome (NS) diseased skin in all affected areas of the body excluding the scalp (the Treatment Area), totaling approximately 50% Body Surface Area (BSA) or more.

Inclusion Criteria:

1. Participant is male or female and at least 4 years of age.
2. Participant has provided written informed consent/assent. Based on the participant's age and local regulations , a participant under legal age of consent must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must provide informed consent for the participant. If a participant reaches the age at which consent is required by local regulations during the study, the participant must provide written informed consent at that time to continue study participation.
3. Female participants must either not have experienced menarche, be postmenopausal , or be surgically sterile , or use a highly effective method of birth control , for the duration of the study and for 3 months following EOT. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test (UPT) at Visit 1/Screening and Visit 2/Baseline. Males must use a condom in addition to having their female partner use a highly effective method of birth control.
4. Participant has a genetically confirmed diagnosis of NS prior to Visit 2/Baseline. Participants without existing results must undergo genetic testing at Visit 1/Screening, which must confirm the diagnosis of NS in order for the participants to be enrolled in the study.

Exclusion Criteria:

1. Participant is pregnant, lactating, or is planning to become pregnant during the study.
2. Participant has active cancer of any type excluding melanoma skin cancer outside of the Treatment Area.
3. Participant has diabetes of any type, except non-insulin dependent diabetes mellitus that is reasonably controlled, in the opinion of the investigator.
4. Participant has evidence of active infection during Screening, or serious infection within 30 days prior to Visit 2/Baseline.
5. Participant has known human immunodeficiency virus, hepatitis B or C virus, or active or latent tuberculosis.
6. Participant has ongoing or recent history of any other uncontrolled and/or clinically significant systemic disease or condition which, in the opinion of the investigator, should exclude participation in the study.
7. Participant has used ultraviolet phototherapy within the Treatment Area within 4 weeks prior to Visit 2/Baseline.
8. Participant has used systemic non-biologics prescription treatment for NS or that in the opinion of the investigator may affect the participant's NS (examples include, but are not limited to antibiotics, retinoids, etc.) within 4 weeks prior to Visit 2/Baseline.
9. Participant has used systemic biologic therapy for NS or that in the opinion of the investigator may affect the participant's NS within 5 half-lives of the biologic therapy prior to Visit 2/Baseline. Published or documented half-life of the product provided by the commercial supplier or Sponsor should be used to establish this value.
10. Participant has used topical prescription treatments, including steroids (examples include, but are not limited to keratolytics, steroids, retinoids, etc.) in the Treatment Area within 2 weeks prior to Visit 2/Baseline.
11. Participant has used any topical bland moisturizers/emollients in the Treatment Area within 24 hours prior to Visit 2/Baseline.
12. Participant is currently enrolled in an investigational drug, biologic, or device study.